Publications by authors named "Marie-Laure Welter"

71 Publications

Role of gastric motility in weight gain after subthalamic nucleus stimulation in Parkinson's disease.

Brain Stimul 2021 Jul-Aug;14(4):801-803. Epub 2021 May 19.

Normandie Univ, UNIROUEN, Inserm U1073, CHU Rouen, Department of Digestive Physiology and CIC-CRB 1404, F-76000, Rouen, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brs.2021.04.027DOI Listing
May 2021

A Causal Role for the Pedunculopontine Nucleus in Human Instrumental Learning.

Curr Biol 2021 03 21;31(5):943-954.e5. Epub 2020 Dec 21.

Motivation, Brain and Behavior (MBB) laboratory, Paris Brain Institute (ICM), Groupe Hospitalier Pitié-Salpêtrière, Paris 75013, France; INSERM Unit 1127, CNRS Unit 7225, Sorbonne Universités (SU), Paris 75005, France. Electronic address:

A critical mechanism for maximizing reward is instrumental learning. In standard instrumental learning models, action values are updated on the basis of reward prediction errors (RPEs), defined as the discrepancy between expectations and outcomes. A wealth of evidence across species and experimental techniques has established that RPEs are signaled by midbrain dopamine neurons. However, the way dopamine neurons receive information about reward outcomes remains poorly understood. Recent animal studies suggest that the pedunculopontine nucleus (PPN), a small brainstem structure considered as a locomotor center, is sensitive to reward and sends excitatory projection to dopaminergic nuclei. Here, we examined the hypothesis that the PPN could contribute to reward learning in humans. To this aim, we leveraged a clinical protocol that assessed the therapeutic impact of PPN deep-brain stimulation (DBS) in three patients with Parkinson disease. PPN local field potentials (LFPs), recorded while patients performed an instrumental learning task, showed a specific response to reward outcomes in a low-frequency (alpha-beta) band. Moreover, PPN DBS selectively improved learning from rewards but not from punishments, a pattern that is typically observed following dopaminergic treatment. Computational analyses indicated that the effect of PPN DBS on instrumental learning was best captured by an increase in subjective reward sensitivity. Taken together, these results support a causal role for PPN-mediated reward signals in human instrumental learning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2020.11.042DOI Listing
March 2021

Nucleus Basalis of Meynert Stimulation for Lewy Body Dementia: A Phase I Randomized Clinical Trial.

Neurology 2021 02 16;96(5):e684-e697. Epub 2020 Nov 16.

From the Departments of Neurology (D.M., D.W., R.L., D.H.), Neurophysiology (J.B., M.-L.W.), and Neurosurgery (S.D.), Rouen University Hospital and University of Rouen; INSERM U1239 (D.M.), Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Mont-Saint-Aignan; Department of Neurology C (T.D., S.T.), Hopital Neurologique Pierre Wertheimer, University of Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Sud Charles Mérieux; Department of Neurology (L.D., K.D.), Lille University Hospital, INSERM 1171; Department of Neurology (J.-L.H.), CIC-INSERM 1402, CHU de Poitiers; Université de Poitiers (J.-L.H.); Department of Neurology (O.G., P.K.), Amiens University Hospital; Department of Neurology (O.M.), Caen University Hospital; Department of Biostatistics (A.G.), Rouen University Hospital; Department of Nuclear Medicine (M.C., P.V.), Henri Becquerel Cancer Center and Rouen University Hospital; and QuantIF-LITIS [EA (Equipe d'Accueil) 4108-FR CNRS 3638] (M.C., P.V.), Faculty of Medicine, University of Rouen, France.

Objectives: Nucleus basalis of Meynert deep brain stimulation (NBM-DBS) has been proposed for patients with dementia. Here, we aim to assess the safety and effects of NBM-DBS in patients with Lewy body dementia (LBD), in a randomized, double-blind, crossover clinical trial.

Methods: Six patients with mild to moderate LBD (mean [SD] age, 62.2 [7.8] years) were included, operated on for bilateral NBM-DBS, and assigned to receive either active or sham NBM-DBS followed by the opposite condition for 3 months. The primary outcome was the difference in the total free recalls of the Free and Cued Selective Reminding Test (FCSRT) between active and sham NBM-DBS. Secondary outcomes were assessments of the safety and effects of NBM-DBS on cognition, motor disability, sleep, and PET imaging.

Results: There was no significant difference in the FCSRT score with active vs sham NBM-DBS. The surgical procedures were well tolerated in all patients, but we observed significant decreases in Stroop and Benton scores after electrode implantation. We observed no significant difference in other scales between active and sham NBM-DBS. With active NBM-DBS relative to baseline, phonemic fluency and motor disability significantly decreased. Lastly, the superior lingual gyrus metabolic activity significantly increased with active NBM-DBS.

Conclusions: NBM-DBS does not appear to be totally safe for patients with LBD with no evidence of cognitive benefit.

Clinicaltrialsgov Identifier: NCT01340001.

Classification Of Evidence: This study provides Class II evidence that, for patients with LBD operated on for bilateral NBM-DBS, active NBM-DBS stimulation compared to sham stimulation did not significantly change selective recall scores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000011227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884989PMC
February 2021

Emotions Modulate Subthalamic Nucleus Activity: New Evidence in Obsessive-Compulsive Disorder and Parkinson's Disease Patients.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 05 11;6(5):556-567. Epub 2020 Aug 11.

Institut du Cerveau et de la Moelle épinière, Institut National de la Santé et de la Recherche Médicale U 1127, Centre National de la Recherche Scientifique unités mixtes de recherche 7225, Sorbonne Université, Paris, France; Neurosurgery Department, Département Médical-Universitaire de Psychiatrie et d'Addictologie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor-Albert Chenevier, Université Paris-Est Créteil, Créteil, France; Department of Mental Health and Psychiatry, Global Health Institute, University of Geneva, Geneva, Switzerland. Electronic address:

Background: Subthalamic nucleus (STN) deep brain stimulation alleviates obsessive-compulsive disorder (OCD) symptoms, suggesting that this basal ganglia structure may play a key role in integrating limbic and motor information. We explored the modulation of STN neural activity by visual emotional information under different motor demands.

Methods: We compared STN local field potentials acquired in 7 patients with OCD and 15 patients with Parkinson's disease off and on levodopa while patients categorized pictures as unpleasant, pleasant, or neutral and pressed a button for 1 of these 3 categories depending on the instruction.

Results: During image presentation, theta power increased for unpleasant compared with neutral images in both patients with OCD and patients with Parkinson's disease. Only in patients with OCD was theta power also increased in pleasant compared with neutral trials. During the button press in patients with OCD, no modification of STN activity was seen on average, but theta power increased when the image triggering the motor response was unpleasant. Conversely, in patients with Parkinson's disease, a beta decrease was observed during the button press unrelated to the valence of the stimulus. Finally, in patients with OCD, a significant positive relationship was observed between the amplitude of the emotionally related theta response and symptom severity (measured using the Yale-Brown Obsessive Compulsive Scale).

Conclusions: We highlighted modulations of STN theta band activity related to emotions that were specific to OCD and correlated with OCD symptom severity. STN theta-induced activity might therefore underlie dysfunction of the limbic STN and its related network leading to OCD pathophysiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bpsc.2020.08.002DOI Listing
May 2021

Deep Brain Stimulation of the Subthalamic, Accumbens, or Caudate Nuclei for Patients With Severe Obsessive-Compulsive Disorder: A Randomized Crossover Controlled Study.

Biol Psychiatry 2021 Nov 2;90(10):e45-e47. Epub 2020 Oct 2.

Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France; Neurosurgery Department, Département Médico-Universitaire de psychiatrie et d'addictologie, Hôpitaux Universitaires Henri Mondor - Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France; Department of Mental Health and Psychiatry, Global Health Institute, University of Geneva, Geneva, Switzerland. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopsych.2020.07.013DOI Listing
November 2021

Early cognitive decline after bilateral subthalamic deep brain stimulation in Parkinson's disease patients with GBA mutations.

Parkinsonism Relat Disord 2020 07 9;76:56-62. Epub 2020 Jun 9.

Sorbonne Université, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Département de Neurologie, Clinical Research Center Neurosciences, Paris, France. Electronic address:

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) has demonstrated its efficacy on motor complications in advanced Parkinson's disease (PD) but does not modify disease progression. Genetic forms of PD have been associated with different cognitive progression profiles.

Objective: To assess the effect of PD-related genetic mutations on cognitive outcome after STN-DBS.

Methods: Patients with STN-DBS were screened for LRRK2, GBA, and PRKN mutations at the Pitié-Salpêtrière Hospital between 1997 and 2009. Patients with known monogenetic forms of PD from six other centers were also included. The Mattis Dementia Rating Scale (MDRS) was used to evaluate cognition at baseline and one-year post-surgery. The standardized Unified PD Rating Scale (UPDRS) evaluation On and Off medication/DBS was also administered. A generalized linear model adjusted for sex, ethnicity, age at onset, and disease duration was used to evaluate the effect of genetic factors on MDRS changes.

Results: We analyzed 208 patients (131 males, 77 females, 54.3 ± 8.8 years) including 25 GBA, 18 LRRK2, 22 PRKN, and 143 PD patients without mutations. PRKN patients were younger and had a longer disease duration at baseline. A GBA mutation was the only significant genetic factor associated with MDRS change (β = -2.51, p = 0.009). GBA mutation carriers had a more pronounced post-operative MDRS decline (3.2 ± 5.1) than patients with LRRK2 (0.9 ± 4.8), PRKN (0.5 ± 2.7) or controls (1.4 ± 4.4). The motor response to DBS was similar between groups.

Conclusion: GBA mutations are associated with early cognitive decline following STN-DBS. Neuropsychological assessment and discussions on the benefit/risk ratio of DBS are particularly important for this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parkreldis.2020.04.002DOI Listing
July 2020

Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome.

Brain 2020 08;143(8):2607-2623

Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, USA.

Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate 'reverse' tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P < 0.017). For centromedial thalamus, connectivity to sensorimotor networks, parietal-temporal-occipital networks, putamen, and cerebellum was positively correlated with tic improvement; the model predicted clinical improvement scores (P = 0.012) and was robust to cross-validation. Regions in the anterior/lateral centromedial thalamus exhibited higher connectivity to the positively correlated networks, but volume of tissue activated overlap with this map did not predict improvement (P > 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awaa188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447520PMC
August 2020

Deep brain activation patterns involved in virtual gait without and with a doorway: An fMRI study.

PLoS One 2019 21;14(10):e0223494. Epub 2019 Oct 21.

Sorbonne Universités, UPMC Univ Paris, CNRS, INSERM, AP HP GH Pitié Salpêtrière, Institut du Cerveau et de la Moelle épinière (ICM), Paris, France.

The human gait program involves many brain areas such as motor cortices, cerebellum, basal ganglia, brainstem, and spinal cord. The mesencephalic locomotor region (MLR), which contains the pedunculopontine (PPN) and cuneiform (CN) nuclei, is thought to be one of the key supraspinal gait generators. In daily life activities, gait primarily occurs in complex conditions, such as through narrow spaces, or while changing direction or performing motor or cognitive tasks. Here, we aim to explore the activity of these subcortical brain areas while walking through narrow spaces, using functional MRI in healthy volunteers and designing a virtual reality task mimicking walking down a hallway, without and with an open doorway to walk through. As a control, we used a virtual moving walkway in the same environment. Twenty healthy volunteers were scanned. Fifteen subjects were selected for second level analysis based on their ability to activate motor cortices. Using the contrast Gait versus Walkway, we found activated clusters in motor cortices, cerebellum, red nucleus, thalamus, and the left MLR including the CN and PPN. Using the contrast Gait with Doorway versus Walkway with Doorway, we found activated clusters in motor cortices, left putamen, left internal pallidum, left substantia nigra, right subthalamic area, and bilateral MLR involving the CN and PPN. Our results suggest that unobstructed gait involves a motor network including the PPN whereas gait through a narrow space requires the additional participation of basal ganglia and bilateral MLR, which may encode environmental cues to adapt locomotion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223494PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802850PMC
March 2020

Accuracy of the robot-assisted procedure in deep brain stimulation.

Int J Med Robot 2019 Dec 11;15(6):e2032. Epub 2019 Sep 11.

Department of Neurosurgery, Rouen University Hospital, Rouen, France.

Introduction: The use of a robot-assisted technology becomes very competitive. The aim of this work was to define the accuracy of robotic assistance in deep brain stimulation surgery and to compare results with that in the literature.

Methods: We retrospectively reviewed the accuracy of lead implantation in 24 consecutive patients who had robot-assisted (ROSA, Zimmer-Biomet) surgery for the treatment of movement disorders. Intended stereotactic coordinates (x, y, z) of contact 0 (the most distal contact at the tip of the electrode) of each definitive lead were compared with actual coordinates obtained by a postoperative CT scan. For each lead, the euclidian 3D distance between the actual and intended location of contact 0 was calculated.

Results: The euclidian 3D distances between the intended and actual location of the contact 0 were 0.81 mm on the right side and 1.12 mm on the left side.

Discussion: Robot-assisted technology for stereotactic surgery is safe and accurate. The association with a 3D flat-panel CT scan is an optimized procedure for deep intracranial electrode implantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rcs.2032DOI Listing
December 2019

Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study.

J Neurol Neurosurg Psychiatry 2019 10 25;90(10):1078-1090. Epub 2019 May 25.

Fixel Institute for Neurological Diseases, Program for Movement Disorders and Neurorestoration, Departments of Neurology and Neurosurgery, University of Florida, Gainesville, Florida, USA.

Background: Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting.

Methods: We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases.

Results: Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi.

Conclusion: The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2019-320379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744301PMC
October 2019

Axial symptoms predict mortality in patients with Parkinson disease and subthalamic stimulation.

Neurology 2019 05 1;92(22):e2559-e2570. Epub 2019 May 1.

From INSERM 1127 (B.L., N.M., Y.A., M.V., C.K., M.-L.W.), Sorbonne Universités, Université Pierre et Marie Curie-Paris Université Paris 06 6, Unité Mixte de Recherche (UMR) S1127, Centre National de la Recherche Scientifique (CNRS), UMR 7225, Institut du Cerveau et de la Moelle Epinière, Paris, France; Department of Neurology (N.M., M.S.), Hôpital Universitaire de Bern, Switzerland; Clinical Investigation Centre (N.M., G.S.), Department of Neurology (V.C., D.G., M.V.), and Department of Neurosurgery (S.N., P.C., C.K.), Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris; and Department of Neurophysiology (M.-L.W.), CHU Charles Nicolle, Rouen University, France.

Objective: To characterize how disease progression is associated with mortality in a large cohort of patients with Parkinson disease (PD) with long-term follow-up after subthalamic nucleus deep brain stimulation (STN-DBS).

Methods: Motor and cognitive disabilities were assessed before and 1, 2, 5, and 10 years after STN-DBS in 143 consecutive patients with PD. We measured motor symptoms "off" and "on" levodopa and STN-DBS and recorded causes of death. We used linear mixed models to characterize symptom progression, including interactions between treatment conditions and time to determine how treatments changed efficacy. We used joint models to link symptom progression to mortality.

Results: Median observation time was 12 years after surgery, during which akinesia, rigidity, and axial symptoms worsened, with mean increases of 8.8 (SD 6.5), 1.8 (3.1), and 5.4 (4.1) points from year 1-10 after surgery ("on" dopamine/"on" STN-DBS), respectively. Responses to dopaminergic medication and STN-DBS were attenuated with time, but remained effective for all except axial symptoms, for which both treatments and their combination were predicted to be ineffective 20 years after surgery. Cognitive status significantly declined. Forty-one patients died, with a median time to death of 9 years after surgery. The current level of axial disability was the only symptom that significantly predicted death (hazard ratio 4.30 [SE 1.50] per unit of square-root transformed axial score).

Conclusions: We quantified long-term symptom progression and attenuation of dopaminergic medication and STN-DBS treatment efficacy in patients with PD and linked symptom progression to mortality. Axial disability significantly predicts individual risk of death after surgery, which may be useful for planning therapeutic strategies in PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000007562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556086PMC
May 2019

Does Bilateral Deep Brain Stimulation of the Subthalamic Nucleus Modify Ano-Rectal Motility in Parkinson's Disease? Results of a Randomized Cross-Over Study.

Neuromodulation 2019 Jun 25;22(4):478-483. Epub 2019 Mar 25.

Nutrition, Gut and Brain Unit (INSERM UMR 1073), Institute for Biomedical Research and innovation, Rouen University, Rouen, France.

Background: Ano-rectal motility impairment is often observed during Parkinson's disease (PD), generating symptoms as constipation and/or incontinence with impaired quality of life. Subthalamic nuclei (STN) deep brain stimulation (DBS) improves motor symptoms of PD, but its effects on anorectal motility are unknown. This study aimed to assess the effects of STN-DBS on the anorectal motility in PD patients, in a randomized cross-over study.

Methods: Sixteen PD patients with bilateral STN-DBS for at least 6 months were included. The anal resting pressure, duration and maximal amplitude of squeeze effort, recto-anal inhibitory reflex, maximal tolerable rectal volume, and anal pressure during defecation effort were measured and compared after STN-DBS was switched OFF and then ON for 2 hours, or vice-versa, in a randomized order.

Key Results: STN-DBS increased maximal amplitude of anal squeezing pressure (OFF: 85.7 ± 14.5 vs ON: 108.4 ± 21.0 cmH O; P = 0.02), with no significant difference in the duration (P = 0.10). No other significant difference was found between stimulation conditions (OFF vs ON) for anal resting pressure (OFF: 72.5 ± 8.6 cmH O vs ON: 71.7 ± 9.0 cmH O; P = 0.24), recto-anal inhibitory reflex, maximal tolerable rectal volume (OFF: 231 ± 24 mL vs ON: 241 ± 26 mL; P = 0.68), or anal pressure during defecation effort with a similar rate of ano-rectal dyssynergia (7/16 and 8/16 with and without STN-DBS, respectively). No order effect (ON-OFF vs OFF-ON) was observed.

Conclusion And Inferences: STN-DBS increased anal squeezing pressure, but did not modify anorectal dyssynergia in PD patients, This study demonstrated the involvement of STN in the voluntary control of anorectal motility in PD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ner.12947DOI Listing
June 2019

Long-term effects of anterior pallidal deep brain stimulation for tourette's syndrome.

Mov Disord 2019 04 20;34(4):586-588. Epub 2019 Feb 20.

STIC: Traitement de la maladie de Gilles de la Tourette par stimulation bilatérale à haute fréquence de la partie antérieure du globus pallidus interne.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.27645DOI Listing
April 2019

White matter tracts lesions and decline of verbal fluency after deep brain stimulation in Parkinson's disease.

Hum Brain Mapp 2019 06 18;40(9):2561-2570. Epub 2019 Feb 18.

Department of Neurology, Rouen University Hospital and University of Rouen, Rouen, France.

Decline of verbal fluency (VF) performance is one of the most systematically reported neuropsychological adverse effects after subthalamic nucleus deep brain stimulation (STN-DBS). It has been suggested that this worsening of VF may be related to a microlesion due to the electrode trajectories. We describe the disruption of surrounding white matter tracts following electrode implantation in Parkinson's disease (PD) patients with STN-DBS and assess whether damage of fiber pathways is associated with VF impairment after surgery. We retrospectively analyzed 48 PD patients undergoing bilateral STN DBS. The lesion mask along the electrode trajectory transformed into the MNI 152 coordinate system, was compared with white matter tract atlas in Tractotron software, which provides a probability and proportion of fibers disconnection. Combining tract- and atlas-based analysis reveals that the trajectory of the electrodes intersected successively with the frontal aslant tract, anterior segment of arcuate tract, the long segment of arcuate tract, the inferior longitudinal fasciculus, the superior longitudinal fasciculus, the anterior thalamic radiation, and the fronto striatal tract. We found no association between the proportion fiber disconnection and the severity of VF impairment 6 months after surgery. Our findings demonstrated that microstructural injury associated with electrode trajectories involved white matter bundles implicated in VF networks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.24544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865750PMC
June 2019

Clinical and anatomical predictors for freezing of gait and falls after subthalamic deep brain stimulation in Parkinson's disease patients.

Parkinsonism Relat Disord 2019 05 24;62:91-97. Epub 2019 Jan 24.

Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épiniere (CRICM), UMR-S975, Paris, France; INSERM, U975, Paris, France; CNRS, UMR 7225, CR-ICM, Paris, France; Neurophysiology Department, CHU Rouen, Normandie University, Rouen, France. Electronic address:

Introduction: Freezing of gait (FOG) and falls are the most disabling motor symptoms in Parkinson's disease (PD) patients. The effects of subthalamic deep-brain-stimulation (STN-DBS) on FOG and falls are still a matter of controversy, and factors contributing to their outcome have yet to be defined.

Methods: We examined the relationship between FOG and falls after STN-DBS and preoperative clinical features, MRI voxel-based-morphometry (VBM) analysis and statistical mapping of electrode locations.

Results: 331 patients (age at surgery = 57.7 ± 8.4 years; disease duration = 12.5 ± 5 years) were included in the final analysis, with VBM analysis in 151 patients. After surgery, FOG was aggravated in 93 patients and falls in 75 patients. After surgery, FOG severity was related to its level before surgery without dopaminergic treatment, the dopaminergic treatment dosage and severity of motor fluctuations after surgery; and falls severity to lower postoperative cognitive performance. VBM analyses revealed that, relative to other patient groups, patients with FOG worsening had putamen grey matter density decrease, and fallers patients a left postcentral gyrus atrophy. The best effects of STN-DBS on FOG and falls were associated with the location of contacts within the STN, but no specific location related to aggravation.

Conclusions: FOG and falls are reduced after STN-DBS in about 1/3 of patients, with the best effects obtained for electrodes located within the STN. Clinicians should be aware that, after STN-DBS, FOG severity is related to preoperative FOG severity whatever its dopa-sensitivity; and falls to lower postoperative cognitive performance; and atrophy of cortico-subcortical brain areas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parkreldis.2019.01.021DOI Listing
May 2019

Functional imaging correlates of akinesia in Parkinson's disease: Still open issues.

Neuroimage Clin 2019 18;21:101644. Epub 2018 Dec 18.

Université de Lyon, Université Claude Bernard Lyon 1, Lyon Neuroscience Research Center, INSERM, U 1028, CNRS, UMR 5292, Neuroplasticity and Neuropathology of Olfactory Perception team, F-69000, Lyon, France. Electronic address:

Akinesia is a major manifestation of Parkinson's disease (PD) related to difficulties or failures of willed movement to occur. Akinesia is still poorly understood and is not fully alleviated by standard therapeutic strategies. One reason is that the area of the clinical concept has blurred boundaries referring to confounded motor symptoms. Here, we review neuroimaging studies which, by providing access to finer-grained mechanisms, have the potential to reveal the dysfunctional brain processes that account for akinesia. It comes out that no clear common denominator could be identified across studies that are too heterogeneous with respect to the clinical/theoretical concepts and methods used. Results reveal, however, that various abnormalities within but also outside the motor and dopaminergic pathways might be associated with akinesia in PD patients. Notably, numerous yet poorly reproducible neural correlates were found in different brain regions supporting executive control by means of resting-state or task-based studies. This includes for instance the dorsolateral prefrontal cortex, the inferior frontal cortex, the supplementary motor area, the medial prefrontal cortex, the anterior cingulate cortex or the precuneus. This observation raises the issue of the multidimensional nature of akinesia. Yet, other open issues should be considered conjointly to drive future investigations. Above all, a unified terminology is needed to allow appropriate association of behavioral symptoms with brain mechanisms across studies. We adhere to a use of the term akinesia restricted to dysfunctions of movement initiation, ranging from delayed response to freezing or even total abolition of movement. We also call for targeting more specific neural mechanisms of movement preparation and action triggering with more sophisticated behavioral designs/event-related neurofunctional analyses. More work is needed to provide reliable evidence, but answering these still open issues might open up new prospects, beyond dopaminergic therapy, for managing this disabling symptom.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2018.101644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412010PMC
December 2019

Normal and pathological neuronal distribution of the human mesencephalic locomotor region.

Mov Disord 2019 02 28;34(2):218-227. Epub 2018 Nov 28.

Sorbonne University, Univ. Pierre & Marie Curie Paris 06, Cnrs, Inserm, AP-HP Pitié-Salpêtrière hospital, Brain and Spinal Cord Institute, Paris, France.

Background: Deep brain stimulation of the pedunculopontine nucleus has been performed to treat dopamine-resistant gait and balance disorders in patients with degenerative diseases. The outcomes, however, are variable, which may be the result of the lack of a well-defined anatomical target.

Objectives: The objectives of this study were to identify the main neuronal populations of the pedunculopontine and the cuneiform nuclei that compose the human mesencephalic locomotor region and to compare their 3-dimensional distribution with those found in patients with Parkinson's disease and progressive supranuclear palsy.

Methods: We used high-field MRI, immunohistochemistry, and in situ hybridization to characterize the distribution of the different cell types, and we developed software to merge all data within a common 3-dimensional space.

Results: We found that cholinergic, GABAergic, and glutamatergic neurons comprised the main cell types of the mesencephalic locomotor region, with the peak densities of cholinergic and GABAergic neurons similarly located within the rostral pedunculopontine nucleus. Cholinergic and noncholinergic neuronal losses were homogeneous in the mesencephalic locomotor region of patients, with the peak density of remaining neurons at the same location as in controls. The degree of denervation of the pedunculopontine nucleus was highest in patients with progressive supranuclear palsy, followed by Parkinson's disease patients with falls.

Conclusions: The peak density of cholinergic and GABAergic neurons was located similarly within the rostral pedunculopontine nucleus not only in controls but also in pathological cases. The neuronal loss was homogeneously distributed and highest in the pedunculopontine nucleus of patients with falls, which suggests a potential pathophysiological link. © 2018 International Parkinson and Movement Disorder Society.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.27578DOI Listing
February 2019

Post mortem high resolution diffusion MRI for large specimen imaging at 11.7 T with 3D segmented echo-planar imaging.

J Neurosci Methods 2019 01 12;311:222-234. Epub 2018 Oct 12.

Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, APHP GH Pitié-Salpêtrière, Institut du cerveau et de la moelle épinière (ICM), F-75013 Paris, France; Centre de Neuro-Imagerie de Recherche (CENIR), Paris, France. Electronic address:

Background: Diffusion weighted imaging (DWI) is the only in vivo technique allowing for the mapping of tissue fiber architecture. Post mortem DWI is an increasingly popular method, since longer acquisition times (compared to in vivo) allow higher spatial and angular resolutions to be achieved. However, DWI protocols must be adapted to post mortem tissue (e.g., tuning acquisition parameters to account for changes in T1/T2). New method: In this work, we developed a framework to obtain high quality diffusion weighted images on post mortem large samples by using a combination of fast imaging with 3D diffusion-weighted segmented EPI (3D-DW seg-EPI), Gadolinium soaking and data denoising. Analyses including tractography were used to check the quality of the acquired data, including a comparison with 3D-DW SE acquisitions. Comparison with existing method: Effects on diffusion data of each of the components of the framework were tested: 3D-DW seg-EPI versus 3D-DW SE EPI; with and without data denoising; with and without Gd-soaking.

Conclusions: Our study demonstrated the feasibility of analysing anatomical connectivity using diffusion imaging of a post mortem macaque brain with a 3D-DW seg-EPI sequence acquired at ultra-high field. The combination of high angular and spatial resolution DWI with Gd-soaking and denoising provided data allowing us to perform diffusion tractography with results very similar to those obtained with a 3D-DW SE acquisition (with shorter acquisition times: 222 h versus 37 h for 3D-DW seg-EPI).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneumeth.2018.10.010DOI Listing
January 2019

Long-term GPi-DBS improves motor features in myoclonus-dystonia and enhances social adjustment.

Mov Disord 2019 01 9;34(1):87-94. Epub 2018 Oct 9.

Sorbonne Université, Faculté de Médecine; CNRS UMR 7225, UMR S 1127, Institut du Cerveau et de la Moelle épinière, Paris, France.

Background: Good short-term results of pallidal deep brain stimulation have been reported in myoclonus-dystonia. Efficacy and safety in the long term remain to be established. In addition, the actual impact of DBS treatment on social inclusion is unknown. The objective of this study was to assess the long-term clinical outcome, quality of life, and social adjustment of GPi-DBS in patients with ε-sarcoglycan (DYT11)-positive myoclonus-dystonia.

Methods: Consecutive myoclonus-dystonia patients with ε-sarcoglycan mutations who underwent GPi-DBS were evaluated at least 5 years postoperatively. Motor symptoms were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale including the Disability Scale, a composite score combining the rest and action parts of the Unified Myoclonus Rating Scale and modified Abnormal Involuntary Movement Scale. Standardized video-protocols were assessed by a blinded and external movement disorder specialist. Social adjustment, cognition, and mood were evaluated.

Results: Nine patients (5 women) with long-term GPi-DBS (8.7 ± 3.1 years) were included. There was significant improvement in the composite myoclonus score (94.1% ± 4% improvement; P = 0.008). Dystonia severity was also markedly improved (71.4% ± 28.33% improvement; P = 0.008) as well as motor disability (88.3% ± 20% improvement; P = 0.008) and abnormal involuntary movement score (71.1% ± 15.0% improvement; P = 0.008). No patients experienced postoperative speech or gait problems or any permanent adverse effects. Eight of the 9 patients had fully enhanced social adjustment and personal achievement, with little or no mood or behavioral disorders.

Conclusions: GPi-DBS seems to be a safe and efficacious treatment for medically refractory ɛ-sarcoglycan myoclonus-dystonia, with sustained motor benefit, good quality of life, and social adjustment in long-term follow-up. © 2018 International Parkinson and Movement Disorder Society.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.27474DOI Listing
January 2019

Decreasing subthalamic deep brain stimulation frequency reverses cognitive interference during gait initiation in Parkinson's disease.

Clin Neurophysiol 2018 11 2;129(11):2482-2491. Epub 2018 Aug 2.

Sorbonne Université, Université Pierre et Marie Curie (UPMC), Université Paris VI, UMR S 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France; Plateforme de physiologie et d'analyse du mouvement (PANAM), Institut du Cerveau et de la Moelle Epinière, ICM, Paris, France; Neurophysiology Department, Centre Hospitalier Universitaire Charles Nicolle, Rouen, France. Electronic address:

Objective: Freezing of gait (FOG) represents a major burden for Parkinson's disease (PD) patients. High-frequency (130-Hz) subthalamic deep-brain-stimulation (STN-DBS) has been reported to aggravate FOG whereas lowering the frequency to 60-80 Hz improves FOG. To further understand the effects of STN-DBS on FOG, we assessed the effects of 80-Hz and 130-Hz STN-DBS on gait initiation performance, in relation to motor and executive function processing.

Methods: Gait initiation was recorded in 19 PD patients and 20 controls, combined or not with a cognitive interference task with a modified Stroop paradigm. PD patients were recorded before surgery with and without dopaminergic treatment, and after surgery with 80-Hz and 130-Hz STN-DBS in a randomised double-blind crossover study.

Results: In the absence of cognitive interference, PD patients exhibited significant gait initiation improvement with dopaminergic treatment, 80-Hz and 130-Hz STN-DBS. Nine patients performed the cognitive interference task. With 130-Hz STN-DBS, all gait initiation parameters were significantly degraded, whereas the cognitive interference task induced no major changes before surgery and with 80-Hz STN-DBS, as in controls.

Conclusions: High-frequency STN-DBS leads to an inability to simultaneously process motor and cognitive information while this ability seems preserved with low-frequency STN-DBS.

Significance: This study supports the potential benefit of 80-Hz STN-DBS on FOG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2018.07.013DOI Listing
November 2018

Extrapyramidal deficits in ALS: a combined biomechanical and neuroimaging study.

J Neurol 2018 Sep 11;265(9):2125-2136. Epub 2018 Jul 11.

Laboratoire CeRSM - EA 2931 Paris Ouest, Nanterre, France.

Introduction: Extrapyramidal deficits are poorly characterised in amyotrophic lateral sclerosis (ALS) despite their contribution to functional disability, increased fall risk and their quality-of-life implications. Given the concomitant pyramidal and cerebellar degeneration in ALS, the clinical assessment of extrapyramidal features is particularly challenging.

Objective: The comprehensive characterisation of postural instability in ALS using standardised clinical assessments, gait analyses and computational neuroimaging tools in a prospective study design.

Methods: Parameters of gait initiation in the anticipatory postural adjustment phase (APA) and execution phase (EP) were evaluated in ALS patients with and without postural instability and healthy controls. Clinical and gait analysis parameters were interpreted in the context of brain imaging findings.

Results: ALS patients with postural instability exhibit impaired gait initiation with an altered APA phase, poor dynamic postural control and significantly decreased braking index. Consistent with their clinical profile, "unsteady" ALS patients have reduced caudate and brain stem volumes compared to "steady" ALS patients.

Interpretation: Our findings highlight that the ALS functional rating scale (ALSFRS-r) does not account for extrapyramidal deficits, which are major contributors to gait impairment in a subset of ALS patients. Basal ganglia degeneration in ALS does not only contribute to cognitive and behavioural deficits, but also adds to the heterogeneity of motor disability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-018-8964-yDOI Listing
September 2018

"The whole perimeter is difficult": Parkinson's disease and the conscious experience of walking in everyday environments.

Disabil Rehabil 2019 11 19;41(23):2784-2791. Epub 2018 Jun 19.

Institut du Cerveau et de la Moelle épinière, Paris, France.

This study sought to characterize the way patients with Parkinson's disease consciously perceive and respond to their surroundings while walking in everyday situations. A qualitative research program designed around an ecological data collection protocol was employed. A convenience sample of 14 patients with a diagnosis of Parkinson's disease and a history of gait difficulties were recruited. Details regarding patients' subjective experience of walking in everyday environments were obtained using first person interviewing techniques with the support of video footage from their daily-life activity. Interview transcripts were analyzed using an interpretive phenomenological approach in order to derive key themes. The sense of proximity and the way in which an individual perceived themselves with respect to their surroundings appeared central to the way patients organized their locomotor behavior. Further to this, the patient relationship to different features and obstacles appeared conditioned by prior experiences in those circumstances. Patients described managing gait difficulties by consciously regulating their walking trajectory and gaze with respect to their environment. Perceptual challenges, visual flow and the dynamic valence of features in the patient's surroundings may have important effects upon the gait stability of patients with Parkinson's disease and warrant further attention in planning rehabilitation interventions.Implications for rehabilitationWalking abilities of patients with Parkinson's disease should be conceptualized in terms of perceptuomotor coupling to a given environment.The functional significance of a patient's environment is dynamic and might be seen to vary in accordance with their physical capacities.Valency, or the subjective relationship between a patient and their surrounds, appears to be an important component of the "fit" between a person and their environment.Novel rehabilitation strategies for the management of parkinsonian gait disturbances might seek to integrate psychological, sensorimotor and environmental elements in order to have individually tailored, ecologically valid home assessment and community rehabilitation programs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09638288.2018.1479779DOI Listing
November 2019

Beta burst coupling across the motor circuit in Parkinson's disease.

Neurobiol Dis 2018 09 20;117:217-225. Epub 2018 Jun 20.

Medical Research Council Brain Network Dynamics Unit, University of Oxford, Oxford, UK; Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK. Electronic address:

Exaggerated activity in the beta band (13-35 Hz) is a hallmark of basal ganglia signals in patients with Parkinson's disease (PD). Beta activity however is not constantly elevated, but comes in bursts. In previous work we showed that the longer beta bursts are maintained, the more the oscillatory synchronisation within the subthalamic nucleus (STN) increases, which is posited to limit the information coding capacity of local circuits. Accordingly, a higher incidence of longer bursts correlates positively with clinical impairment, while the opposite is true for short, more physiological bursts. Here, we test the hypothesis that beta bursts not only indicate local synchronisation within the STN, but also phasic coupling across the motor network and hence entail an even greater restriction of information coding capacity in patients with PD. Local field potentials from the subthalamic nucleus and EEG over the motor cortex area were recorded in nine PD patients after temporary lead externalization after surgery for deep brain stimulation and overnight withdrawal of levodopa. Beta bursts were defined as periods exceeding the 75th percentile of signal amplitude and the coupling between bursts was considered using two distinct measurements, first the % overlapping (%OVL) as a feature of the amplitude coupling and secondly the phase synchrony index (PSI) to measure the phase coupling between regions. %OVL between STN and cortex and between the left and the right STN was higher than expected between the regions than if they had been independent. Similarly, PSI was higher during bursts as opposed to non-bursts periods. In addition, %OVL was greater for long compared to short bursts. Our results support the hypothesis that beta bursts involve long-range coupling between structures in the basal ganglia-cortical network. The impact of this is greater during long as opposed to short duration beta bursts. Accordingly, we posit that episodes of simultaneously elevated coupling across multiple structures in the basal ganglia-cortical circuit further limit information coding capacity and may have further impact upon motor impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nbd.2018.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054304PMC
September 2018

The feasibility and positive effects of a customised videogame rehabilitation programme for freezing of gait and falls in Parkinson's disease patients: a pilot study.

J Neuroeng Rehabil 2018 04 10;15(1):31. Epub 2018 Apr 10.

CNRS, UMR7225, Institut du Cerveau et de la Moelle Epinière, Sorbonne universités, Université Pierre et Marie Curie (UPMC) Paris P6; UMRS 1127, 75013, Paris, France.

Background: Freezing of gait and falls represent a major burden in patients with advanced forms of Parkinson's disease (PD). These axial motor signs are not fully alleviated by drug treatment or deep-brain stimulation. Recently, virtual reality has emerged as a rehabilitation option for these patients. In this pilot study, we aim to determine the feasibility and acceptability of rehabilitation with a customised videogame to treat gait and balance disorders in PD patients, and assess its effects on these disabling motor signs.

Methods: We developed a customised videogame displayed on a screen using the Kinect system. To play, the patient had to perform large amplitude and fast movements of all four limbs, pelvis and trunk, in response to visual and auditory cueing, to displace an avatar to collect coins and avoid obstacles to gain points. We tested ten patients with advanced forms of PD (median disease duration = 16.5 years) suffering from freezing of gait and/or falls (Hoehn&Yahr score ≥ 3) resistant to antiparkinsonian treatment and deep brain stimulation. Patients performed 18 training sessions during a 6-9 week period. We measured the feasibility and acceptability of our rehabilitation programme and its effects on parkinsonian disability, gait and balance disorders (with clinical scales and kinematics recordings), positive and negative affects, and quality of life, after the 9th and 18th training sessions and 3 months later.

Results: All patients completed the 18 training sessions with high feasibility, acceptability and satisfaction scores. After training, the freezing-of-gait questionnaire, gait-and-balance scale and axial score significantly decreased by 39, 38 and 41%, respectively, and the activity-balance confidence scale increased by 35%. Kinematic gait parameters also significantly improved with increased step length and gait velocity and decreased double-stance time. Three months after the final session, no significant change persisted except decreased axial score and increased step length and velocity.

Conclusions: This study suggests that rehabilitation with a customised videogame to treat gait and balance disorders is feasible, well accepted, and effective in parkinsonian patients. These data serve as preliminary evidence for further larger and controlled studies to propose this customised videogame rehabilitation programme at home.

Trial Registration: ClinicalTrials.gov NCT02469350 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12984-018-0375-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894136PMC
April 2018

Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry.

JAMA Neurol 2018 03;75(3):353-359

Maastricht University Medical Center, Maastricht, the Netherlands; MHeNs, Experimental Neurosurgery, Maastricht University, Maastricht, the Netherlands.

Importance: Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome.

Objective: To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome.

Design, Setting, And Participants: The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide.

Exposures: Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]).

Main Outcomes And Measures: Scores on the Yale Global Tic Severity Scale and adverse events.

Results: The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P < .001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P < .001), and the mean (SD) phonic tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P < .001). The overall adverse event rate was 35.4% (56 of 158 patients), with intracranial hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events (3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation-induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]).

Conclusions And Relevance: Deep brain stimulation was associated with symptomatic improvement in patients with Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaneurol.2017.4317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885852PMC
March 2018

Contribution of the supplementary motor area and the cerebellum to the anticipatory postural adjustments and execution phases of human gait initiation.

Neuroscience 2017 09 1;358:181-189. Epub 2017 Jul 1.

Université Pierre et Marie Curie-Paris 6, Institut du Cerveau et de la Moelle épiniere (ICM), UMR-S975, Paris, France; Inserm, U975, Paris, France; CNRS, UMR 7225, Paris, France; Plateforme d'Analyse du Mouvement (PANAM-CENIR), Institut du Cerveau et de la Moelle Epinière, Paris, France; Centre d'Investigation Clinique, Hôpitaux Universitaires Pitié-Salpêtrière/Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France; Département de Neurologie, Hôpitaux Universitaires Pitié-Salpêtrière/Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France. Electronic address:

Several brain structures including the brainstem, the cerebellum and the frontal cortico-basal ganglia network, with the primary and premotor areas have been shown to participate in the functional organization of gait initiation and postural control in humans, but their respective roles remain poorly understood. The aim of this study was to better understand the role of the supplementary motor area (SMA) and posterior cerebellum in the gait initiation process. Gait initiation parameters were recorded in 22 controls both before and after continuous theta burst transcranial stimulation (cTBS) of the SMA and cerebellum, and were compared to sham stimulation, using a randomized double-blind design study. The two phases of gait initiation process were analyzed: anticipatory postural adjustments (APAs) and execution, with recordings of soleus and tibialis anterior muscles. Functional inhibition of the SMA led to a shortened APA phase duration with advanced and increased muscle activity; during execution, it also advanced muscle co-activation and decreased the duration of stance soleus activity. Cerebellar functional inhibition did not influence the APA phase duration and amplitude but increased muscle co-activation, it decreased execution duration and showed a trend to increase velocity, with increased swing soleus muscle duration and activity. The results suggest that the SMA contributes to both the timing and amplitude of the APAs with no influence on step execution and the posterior cerebellum in the coupling between the APAs and execution phases and leg muscle activity pattern during gait initiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroscience.2017.06.047DOI Listing
September 2017

Anterior pallidal deep brain stimulation for Tourette's syndrome: a randomised, double-blind, controlled trial.

Lancet Neurol 2017 08 20;16(8):610-619. Epub 2017 Jun 20.

Department of Neurology, Nantes University Hospital, Nantes, France.

Background: Deep brain stimulation (DBS) has been proposed to treat patients with severe Tourette's syndrome, and open-label trials and two small double-blind trials have tested DBS of the posterior and the anterior internal globus pallidus (aGPi). We aimed to specifically assess the efficacy of aGPi DBS for severe Tourette's syndrome.

Methods: In this randomised, double-blind, controlled trial, we recruited patients aged 18-60 years with severe and medically refractory Tourette's syndrome from eight hospitals specialised in movement disorders in France. Enrolled patients received surgery to implant bilateral electrodes for aGPi DBS; 3 months later they were randomly assigned (1:1 ratio with a block size of eight; computer-generated pairwise randomisation according to order of enrolment) to receive either active or sham stimulation for the subsequent 3 months in a double-blind fashion. All patients then received open-label active stimulation for the subsequent 6 months. Patients and clinicians assessing outcomes were masked to treatment allocation; an unmasked clinician was responsible for stimulation parameter programming, with intensity set below the side-effect threshold. The primary endpoint was difference in Yale Global Tic Severity Scale (YGTSS) score between the beginning and end of the 3 month double-blind period, as assessed with a Mann-Whitney-Wilcoxon test in all randomly allocated patients who received active or sham stimulation during the double-blind period. We assessed safety in all patients who were enrolled and received surgery for aGPi DBS. This trial is registered with ClinicalTrials.gov, number NCT00478842.

Findings: Between Dec 6, 2007, and Dec 13, 2012, we enrolled 19 patients. We randomly assigned 17 (89%) patients, with 16 completing blinded assessments (seven [44%] in the active stimulation group and nine [56%] in the sham stimulation group). We noted no significant difference in YGTSS score change between the beginning and the end of the 3 month double-blind period between groups (active group median YGTSS score 68·5 [IQR 34·0 to 83·5] at the beginning and 62·5 [51·5 to 72·0] at the end, median change 1·1% [IQR -23·9 to 38·1]; sham group 73·0 [69·0 to 79·0] and 79·0 [59·0 to 81·5], median change 0·0% [-10·6 to 4·8]; p=0·39). 15 serious adverse events (three in patients who withdrew before stimulation and six each in the active and sham stimulation groups) occurred in 13 patients (three who withdrew before randomisation, four in the active group, and six in the sham group), with infections in DBS hardware in four patients (two who withdrew before randomisation, one in the sham stimulation group, and one in the active stimulation group). Other serious adverse events included one electrode misplacement (active stimulation group), one episode of depressive signs (active stimulation group), and three episodes of increased tic severity and anxiety (two in the sham stimulation group and one in the active stimulation group).

Interpretation: 3 months of aGPi DBS is insufficient to decrease tic severity for patients with Tourette's syndrome. Future research is needed to investigate the efficacy of aGPi DBS for patients over longer periods with optimal stimulation parameters and to identify potential predictors of the therapeutic response.

Funding: French Ministry of Health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1474-4422(17)30160-6DOI Listing
August 2017

A Selective Role for Dopamine in Learning to Maximize Reward But Not to Minimize Effort: Evidence from Patients with Parkinson's Disease.

J Neurosci 2017 06 24;37(25):6087-6097. Epub 2017 May 24.

Motivation, Brain and Behavior Laboratory, Brain and Spine Institute, Paris, 75013, France,

Instrumental learning is a fundamental process through which agents optimize their choices, taking into account various dimensions of available options such as the possible reward or punishment outcomes and the costs associated with potential actions. Although the implication of dopamine in learning from choice outcomes is well established, less is known about its role in learning the action costs such as effort. Here, we tested the ability of patients with Parkinson's disease (PD) to maximize monetary rewards and minimize physical efforts in a probabilistic instrumental learning task. The implication of dopamine was assessed by comparing performance ON and OFF prodopaminergic medication. In a first sample of PD patients ( = 15), we observed that reward learning, but not effort learning, was selectively impaired in the absence of treatment, with a significant interaction between learning condition (reward vs effort) and medication status (OFF vs ON). These results were replicated in a second, independent sample of PD patients ( = 20) using a simplified version of the task. According to Bayesian model selection, the best account for medication effects in both studies was a specific amplification of reward magnitude in a Q-learning algorithm. These results suggest that learning to avoid physical effort is independent from dopaminergic circuits and strengthen the general idea that dopaminergic signaling amplifies the effects of reward expectation or obtainment on instrumental behavior. Theoretically, maximizing reward and minimizing effort could involve the same computations and therefore rely on the same brain circuits. Here, we tested whether dopamine, a key component of reward-related circuitry, is also implicated in effort learning. We found that patients suffering from dopamine depletion due to Parkinson's disease were selectively impaired in reward learning, but not effort learning. Moreover, anti-parkinsonian medication restored the ability to maximize reward, but had no effect on effort minimization. This dissociation suggests that the brain has evolved separate, domain-specific systems for instrumental learning. These results help to disambiguate the motivational role of prodopaminergic medications: they amplify the impact of reward without affecting the integration of effort cost.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.2081-16.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596498PMC
June 2017

Tackling psychosocial maladjustment in Parkinson's disease patients following subthalamic deep-brain stimulation: A randomised clinical trial.

PLoS One 2017 11;12(4):e0174512. Epub 2017 Apr 11.

Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for the motor and non-motor signs of Parkinson's disease (PD), however, psychological disorders and social maladjustment have been reported in about one third of patients after STN-DBS. We propose here a perioperative psychoeducation programme to limit such social and familial disruption.

Methods: Nineteen PD patients and carers were included in a randomised single blind study. Social adjustment scale (SAS) scores from patients and carers that received the psychoeducation programme (n = 9) were compared, both 1 and 2 years after surgery, with patients and carers with usual care (n = 10). Depression, anxiety, cognitive status, apathy, coping, parkinsonian disability, quality-of-life, carers' anxiety and burden were also analysed.

Results: Seventeen patients completed the study, 2 were excluded from the final analysis because of adverse events. At 1 year, 2/7 patients with psychoeducation and 8/10 with usual care had an aggravation in at least one domain of the SAS (p = .058). At 2 years, only 1 patient with psychoeducation suffered persistent aggravated social adjustment as compared to 8 patients with usual care (p = .015). At 1 year, anxiety, depression and instrumental coping ratings improved more in the psychoeducation than in the usual care group (p = .038, p = .050 and p = .050, respectively). No significant differences were found between groups for quality of life, cognitive status, apathy or motor disability.

Conclusions: Our results suggest that a perioperative psychoeducation programme prevents social maladjustment in PD patients following STN-DBS and improves anxiety and depression compared to usual care. These preliminary data need to be confirmed in larger studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174512PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388322PMC
September 2017
-->